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Published on: February 9, 2016
Generation of LAK cells in vitro in patients with acute leukemia
A Parrado1, J M Rodriguez-Fernandez, S Casares
1Servicio de Hematología y Hemoterapia, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Insights
Interleukin-2 (IL-2) activated killer (LAK) cells show tumoricidal potential. While LAK cells were effective in normal donors, their efficacy was reduced in acute leukemia patients post-chemotherapy or bone marrow transplant, suggesting IL-2 therapy for minimal residual disease.
Area of Science:
- Immunology
- Oncology
Background:
- Interleukin-2 (IL-2) stimulation of lymphocytes generates lymphokine-activated killer (LAK) cells with tumoricidal potential.
- Acute leukemia patients often have impaired immune function after chemotherapy (CT) or autologous bone marrow transplantation (ABMT).
Purpose of the Study:
- To evaluate the cytolytic capacity of LAK cells in acute leukemia patients in complete remission (CR) after CT and ABMT compared to normal donors.
- To assess the potential of IL-2 therapy for targeting minimal residual leukemia.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from 51 post-CT patients, 24 post-ABMT patients, and 44 normal donors were stimulated with IL-2 to generate LAK cells.
- The cytolytic activity of both non-activated PBMCs and LAK cells against blast cells and K562 (natural killer - NK activity) was measured.
- Patients with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) were included.
Main Results:
- Non-activated PBMCs showed minimal lysis (<10%) in normal donors and were negative in 95% of post-CT patients.
- LAK cells demonstrated positive results in 82% of normal donors but only 37.5% of post-CT patients.
- Natural killer (NK) activity was reduced in post-CT and post-ABMT patients compared to normal donors. LAK cells from 25% of post-CT patients lacked significant activity, while 75% showed some activity.
Conclusions:
- LAK cell activity is significantly reduced in acute leukemia patients post-treatment.
- Despite reduced efficacy, the results support the use of IL-2-activated killer cells as a potential treatment against minimal residual leukemia.
Abstract:
The in vitro stimulation of lymphocytes with interleukin-2 (IL-2) generates lymphokine-activated killer (LAK) cells with tumoricidal potential. In this work we studied the cytolytic capacity of LAK cells in 51 acute leukemia patients in complete remission (CR) after chemotherapy (CT), in 24 acute leukemia patients who had undergone autologous bone marrow transplantation (ABMT), and in a control group of 44 normal donors. In the normal donor control group the effect of non-IL-2-activated peripheral blood mononuclear cells (PBMC) against blast cells was always lower than 10% lysis, which we have taken as a lower limit for positive results. In 95% of post-CT patients, the lytic effect of PBMC was negative. LAK cells produced positive results in 82% of normal donors and in 37.5% of post-CT patients. The effect of PBMC against K562, i.e. natural killer (NK) activity, in post-CT patients as well as in post-ABMT patients was reduced in comparison with the average for normal donors. LAK cells from 25% of post-CT patients had no notable activity against K562 or Raji, nor was there any positive effect against autologous blast cells. In the rest (75%), one-half generated positive activity. We did not observe any correlation between lytic activity in PBMCs or in LAK cells, nor did we observe significant differences between lytic activity in patients with acute lymphoblastic leukemia (ALL) and those with acute myeloblastic leukemia (AML), or between patients who had undergone CT and those receiving ABMTs. These results support the use of IL-2 as a treatment against minimal residual leukemia.
